Practical Considerations for Administering Letermovir

Robert J. Soiffer, MD: How do you think letermovir might be used in the future at your institution?

Genovefa Papanicolaou, MD: Patients that come for transplant are very heterogenous. They get different types of grafts, they develop different complications, and the risk of CMV (cytomegalovirus) varies among these groups and also during the time after transplant. The fairly high-risk groups clearly benefit from prevention. And certainly, at our institution, we will provide letermovir to high risk groups.
In this trial, interestingly, the majority of the patients were at standard risk. About 70% of the patients in the trial were low risk. The trial demonstrated that there was a substantial benefit for patients at low risk. So, eventually, everybody would benefit from letermovir. We plan to use it for everybody at our institution. So, even though we have the high-risk patients in mind, we recognize that it was useful for all patients.

Robert J. Soiffer, MD: How is letermovir given? Is it oral and intravenous?

Genovefa Papanicolaou, MD: There is an oral form and an intravenous form. That’s very important because it allows letermovir to be started very early after transplant. In the trial, the median time from transplant to starting letermovir was 9 days. About 60% of patients in the trial started letermovir before 2 weeks after transplant. And so, the availability of the intravenous formulation allows patients with mucositis, patients that cannot tolerate oral medications, to start letermovir early.

Robert J. Soiffer, MD: On that trial, patients could start letermovir right after day 0 or day 1. They could go out to day 22 or 23. What is your feeling about what the ideal time to start letermovir might be?

Genovefa Papanicolaou, MD: That’s a very good question. The trial had a very large window for starting from day 0, from the day of the stem cell infusion, up to day 28, as long as the patients did not have CMV infection. We know a little about when CMV infection occurs. In the T-cell depleted patient, CMV infections usually occur early. And so, there is a bigger need to start letermovir early.
Cord blood patients tend to reactivate later. So, if we go by the trial of having just a negative PCR, perhaps you can say that you can start later in certain groups. However, a fact for all CMV prevention is that the earlier you start the prevention the more effective it is. Given the population of the phase III trial, I would say that it’s important to start before the 2 weeks.

Robert J. Soiffer, MD: To clarify one other point, and you mentioned this early on, the patients included in this trial were those who were CMV-seropositive? In other words, CMV-seronegative recipients were not eligible to go on this trial?

Genovefa Papanicolaou, MD: Correct.

Robert J. Soiffer, MD: There aren’t that many drug interactions, but there’s an odd interaction with cyclosporine. Perhaps you could describe this, in terms of dosing?

Genovefa Papanicolaou, MD: Yes. Patients who are on cyclosporine only require half the dose of letermovir that is given to other patients. The standard dose is 480 mg once a day. Patients with cyclosporine get 240 mg once a day due to the interaction of letermovir with cyclosporine. Now, thankfully, the level of the immunosuppressant is monitored routinely in every institution, so it should not be a problem.

Robert J. Soiffer, MD: Right.

Transcript Edited for Clarity

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Transcript:

Robert J. Soiffer, MD: How do you think letermovir might be used in the future at your institution?

Genovefa Papanicolaou, MD: Patients that come for transplant are very heterogenous. They get different types of grafts, they develop different complications, and the risk of CMV (cytomegalovirus) varies among these groups and also during the time after transplant. The fairly high-risk groups clearly benefit from prevention. And certainly, at our institution, we will provide letermovir to high risk groups.
In this trial, interestingly, the majority of the patients were at standard risk. About 70% of the patients in the trial were low risk. The trial demonstrated that there was a substantial benefit for patients at low risk. So, eventually, everybody would benefit from letermovir. We plan to use it for everybody at our institution. So, even though we have the high-risk patients in mind, we recognize that it was useful for all patients.

Robert J. Soiffer, MD: How is letermovir given? Is it oral and intravenous?

Genovefa Papanicolaou, MD: There is an oral form and an intravenous form. That’s very important because it allows letermovir to be started very early after transplant. In the trial, the median time from transplant to starting letermovir was 9 days. About 60% of patients in the trial started letermovir before 2 weeks after transplant. And so, the availability of the intravenous formulation allows patients with mucositis, patients that cannot tolerate oral medications, to start letermovir early.

Robert J. Soiffer, MD: On that trial, patients could start letermovir right after day 0 or day 1. They could go out to day 22 or 23. What is your feeling about what the ideal time to start letermovir might be?

Genovefa Papanicolaou, MD: That’s a very good question. The trial had a very large window for starting from day 0, from the day of the stem cell infusion, up to day 28, as long as the patients did not have CMV infection. We know a little about when CMV infection occurs. In the T-cell depleted patient, CMV infections usually occur early. And so, there is a bigger need to start letermovir early.
Cord blood patients tend to reactivate later. So, if we go by the trial of having just a negative PCR, perhaps you can say that you can start later in certain groups. However, a fact for all CMV prevention is that the earlier you start the prevention the more effective it is. Given the population of the phase III trial, I would say that it’s important to start before the 2 weeks.

Robert J. Soiffer, MD: To clarify one other point, and you mentioned this early on, the patients included in this trial were those who were CMV-seropositive? In other words, CMV-seronegative recipients were not eligible to go on this trial?

Genovefa Papanicolaou, MD: Correct.

Robert J. Soiffer, MD: There aren’t that many drug interactions, but there’s an odd interaction with cyclosporine. Perhaps you could describe this, in terms of dosing?

Genovefa Papanicolaou, MD: Yes. Patients who are on cyclosporine only require half the dose of letermovir that is given to other patients. The standard dose is 480 mg once a day. Patients with cyclosporine get 240 mg once a day due to the interaction of letermovir with cyclosporine. Now, thankfully, the level of the immunosuppressant is monitored routinely in every institution, so it should not be a problem.